In the double-blind trial, 616 patients from 118 sites in 16 countries who had no sensitizing EGFR or ALK mutations and had received no previous treatment for metastatic disease were randomized 2:1 between February 2016 and March 2017 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks for up to 35 cycles plus chemotherapy. Chemotherapy consisted of 4 cycles of investigator’s choice of cisplatin 75 mg/m2 or carboplatin AUC = 5 plus pemetrexed (Alimta) 500 mg/m2 every 3 weeks followed by pemetrexed maintenance at 500 mg/m2 every 3 weeks. Randomization was stratified by programmed cell death ligand 1 (PD-L1) expression (≥ 1% vs < 1%), choice of platinum drug, and smoking history. Crossover to pembrolizumab monotherapy was permitted for placebo patients with disease progression.

Grade ≥ 3 adverse events occurred in 67.2% of the pembrolizumab group and 65.8% of the placebo group, with the most common in the pembrolizumab group being anemia (16.3% vs 15.3%) and neutropenia (15.8% vs 11.9%). Acute kidney injury was more common in the pembrolizumab group (5.2% vs 0.5%; grade ≥ 3 in 2.0%) and led to discontinuation of all study drugs in 2.0% of pembrolizumab patients. Immune-mediated adverse events occurred in 22.7% vs 11.9% of patients and were grade ≥ 3 in 8.9% vs 4.5%. Adverse events led to discontinuation of all study drugs in 13.8% vs 7.9% of patients and to pembrolizumab and placebo in 20.2% vs 10.4%. Adverse events led to death in 6.7% vs 5.9% of patients. Three immune-mediated adverse events (all cases of pneumonitis) led to death in the pembrolizumab group.

The investigators concluded, “In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.”

The study was funded by Merck.

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